Childhood asthma linked to infection during pregnancy

Babies born prematurely and exposed before birth to a bacterial infection of the placenta could have an increased risk for developing asthma by age 8. That’s what researchers reported in a recent issue of Archives of Pediatrics & Adolescent Medicine.

Children exposed to the bacterial infection and born prematurely at 23 to 36 weeks gestation were diagnosed with asthma about three times more often than those delivered after a full-term birth.

The bacterial infection, called chorioamnionitis, is a complication of pregnancy that affects the mother’s placenta and amniotic fluid. More than half of all premature births are thought to be associated with this infection. It is a major cause of maternal, fetal and neonatal complications including stillbirth and neonatal intensive care unit (NICU) admissions.

Evidence from previous studies indicated lasting injuries to the preterm infants’ lung tissue as a result of being exposed to the bacterial infection. However, the link to childhood asthma had not been determined. That was the purpose of this study.

Rates of childhood asthma

The U.S. Department of Health and Human Services notes that asthma is the most common chronic childhood disease. In 2006, nearly 10 million children under the age of 18 had been diagnosed with asthma. The rate is highest among American Indian, Alaskan Native and African American children.

Childhood asthma is considered a major public health problem because of high rates of emergency room visits, learning problems, missed school days and general disruption to a child’s life.

What the study found

The study found that children exposed to the chorioamnionitis bacterial infection and born prematurely at 23 to 36 weeks gestation were diagnosed with asthma about three times more often than those delivered after a full-term birth. Further analysis showed that those exposed to the infection were at higher risk for asthma when compared with specific gestational age categories of children who were not exposed (1.23-fold increased risk for 23-28 weeks of gestational age; 1.51-fold increased risk for 28-33 weeks; and 1.26-fold increased risk for 34-36 weeks).

The effects of chorioamnionitis on childhood asthma differed by race and ethnicity, with children born to African American women at higher risk.

And, the association between chorioamnionitis and asthma in babies born prematurely persisted even after researchers adjusted for other possible contributing factors such as a mother’s age, race or ethnicity; mother’s smoking during pregnancy; prenatal care; whether the mother had asthma; and whether the infant had a respiratory problem called bronchopulmonary dysplasia.

“Chorioamnionitis and preterm gestation may result in increased risk of childhood asthma, presumably in response to inflammation-mediated fetal lung injury and/or heightened immune response against subsequent encounters with pathogens,” the researchers concluded.

How the study was done

Darios Getahun, MD, MPH, and associates at Kaiser Permanente Department of Research and Evaluation in Pasadena reviewed Kaiser’s records on 510,216 children born at the organization’s hospitals in Southern California between 1991 and 2007. The retrospective study used Kaiser’s Matched Perinatal Records that match all births at their hospitals with maternal and infant hospitalizations, outpatient physician encounters, and pharmacy records. Only pregnancies that lasted 23 or more weeks were included. Excluded were stillbirths, induced and spontaneous terminations, children with birth defects, and neonatal mortality cases. The total number of children included in the final analysis was 397,852.

Study limitations

The study does not establish chorioamnionitis as a cause of childhood asthma, but it does show a strong link. Researchers noted that the study looked at clinical diagnoses of chorioamnionitis; however, there may have been many cases never diagnosed because of the absence of symptoms. Also, there may be other unmeasured factors such as exposure to other types of infections during pregnancy that moderated the association between chorioamnionitis and childhood asthma. Mothers could have underreported their use of tobacco during pregnancy. These factors could have affected the researchers’ estimates.

For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.

Page last updated: 4/21/2015 9:06:00 AM

What the news means for you

Study may help doctors identify children at risk for asthma

Hubert O. Ballard, MDNeonatologist

This study is potentially helpful in identifying early on children who could be at an increased risk for developing asthma. However, the study looked only at a unique population of premature babies born to women who had symptoms that had been clinically diagnosed as chorioamnionitis during pregnancy. It did not consider subclinical patients – those mothers who had no symptoms but who have had the infection, which is estimated to affect 40 to 60 percent of preterm infants.

“Once the unborn baby’s lungs have been exposed to this inflammation, the infant may be predisposed to respiratory diseases such as childhood asthma.”

The exclusion of this group of patients and their babies makes it more difficult to determine the role of chorioamnionitis during pregnancy with childhood asthma. I also question how well the researchers filtered out the effects of any type of lung injury that occurred from the infant’s premature birth, such as severity of bronchopulmonary dysplasia. Overall, though, this is the first study with a large enough sample size to show a pretty clear association between clinically diagnosed chorioamnionitis and premature births with the development of childhood asthma.

What is most interesting is that even those babies who made it to full-term deliveries and who were exposed to chorioamnionitis were more likely to develop asthma. The study tells us that the development of asthma is probably a very early event; once the unborn baby’s lungs have been exposed to this inflammation, the infant could be predisposed to respiratory diseases such as childhood asthma.

These findings are not surprising. This is further support for the Barker Hypothesis that suggests an association between several adult diseases, such as obesity, hypertension and diabetes. The theory says that some babies are “programmed” early on to be more at risk for developing these diseases because of what they are exposed to during the pregnancy.

What should parents know?

When we counsel parents about their prematurely born infants in our Neonatal Intensive Care Unit (NICU) at Kentucky Children’s Hospital, they ask us about the potential for long-term problems. My colleagues and I agree that the most common problem these infants will have is with their lungs. Knowing the findings of this study will help us guide them and their children’s pediatricians in being more vigilant so they can catch and treat the asthma early on.

Unfortunately, other than good prenatal care, there is not much a woman can do to prevent herself from acquiring this infection during her pregnancy. Premature babies born without prenatal care tend not to do as well as those whose mothers did seek medical care during their pregnancy.

Not a lot is known about how chorioamnionitis develops or where it comes from. Obstetricians are very astute in watching for this infection and treating it with antibiotics. If there is a concern that a baby will be born prematurely, we can minimize overall damage to the baby’s lungs by giving it steroids. Also, if a baby is at risk of developing asthma or other lung ailments, parents can take steps to minimize that risk by not smoking or exposing the infant to second-hand smoke.

“[This new study] adds fuel to the fire in support of a woman getting good prenatal care to pick up on conditions that, if left untreated, could affect her baby’s health later in life.”

Bronchopulmonary dysplasia

At Kentucky Children’s Hospital we’ve done a lot of research on a lung condition known as bronchopulmonary dysplasia – the leading cause of death in babies born prematurely. Because their lungs haven’t had a chance to develop completely before birth, premature babies are more apt to have difficulty breathing, lung infections and to develop conditions such as asthma later in life. We just completed the largest single-center study treating premature infants with azithromycin, an antibiotic, attempting to prevent the lung problems that premature infants develop. Our study demonstrated a possible benefit in the treatment of preterm infants with azithromycin who are colonized (infected) with Ureaplasma species.

The bottom line is that this new study is interesting. It adds fuel to the fire in support of a woman getting good prenatal care to pick up on conditions that, if left untreated, could affect her baby’s health later in life.

Dr. Ballard, neonatologist, is an associate professor at UK HealthCare.

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